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The Varroa destructor mite has become the greatest threat to Apis mellifera health worldwide while rarely causing serious damage to its native hosts Apis cerana.Understanding of the resistant mechanisms of Eastern bees against Varroa mites will help researchers determine how to protect other species from them.The A.cerana genome has not been sequenced,so here we sequenced the A.cerana nurse workers transcriptome using the Illumina Solexa sequencing method and monitored the differential gene expression of A.cerana bees challenged by V.destructor.Using de novo transcriptome assembly,we obtained 91,172 unigenes (transcripts) for A.cerana.Differences in gene expression levels between the unchallenged (Con) and challenged (Con2) samples were estimated,and total of 36,691 transcripts had at least a two-fold difference between the two libraries.272 differentially expressed genes had differences > 15-fold,and 265 unigenes were present at higher levels in Con2 than in Con.Among the upregulated unigenes in the Con2 colony,genes related to skeletal muscle movement (Troponin and calcium-transporting ATPase),olfactory sensitivity (odorant binding proteins,and Down syndrome cell adhesion molecule gene) and transcription factors(cyclic adenosine monophosphate-responsive element-binding protein and transcription factor mblk-1) appeared to be involved in Varroa resistance.Real-time PCR was performed to validate these differentially expressed genes screened out by the sequencing approach and sufficient consistency was observed between the two methods.These findings strongly support that hygienic and grooming behaviors play the most important role in Varroa resistance.